Molecular Pharmacology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
Department of Pharmacy, Daffodil International University, Dhanmondi-27, Dhaka 1209, Bangladesh.
Eur J Pharmacol. 2021 Aug 5;904:174166. doi: 10.1016/j.ejphar.2021.174166. Epub 2021 May 9.
Pyroptosis has recently been established as a term of programmed-inflammatory cell death. Pyroptosis is mainly divided into two molecular signaling pathways, including caspase-1-dependent canonical and caspase-4/5/11-dependent non-canonical inflammasome pathways. Extensive investigations have reported inflammasome activation facilitates the maturation and secretion of the inflammatory factors interleukin-1β/18 (IL-1β/18), cleavage of gasdermin D (GSDMD), and leading to the stimulation of pyroptosis-mediated cell death. Furthermore, accumulating studies report NLRP3 inflammasome activation plays a significant role in triggering the pyroptosis-mediated cell death and promotes the pathogenesis of diabetic retinopathy (DR). Our current review elaborates on the molecular mechanisms of pyroptosis-signaling pathways and their potential roles in the pathogenesis and impact of DR development. We also emphasize several investigational molecules regulating key steps in pyroptotic-cell death to create new comprehensions and findings to explore the pathogenesis of DR advancement. Our narrative review concisely suggests these potential pharmacological agents could be promising therapies to treat and manage DR in the future.
细胞焦亡最近被确立为一种程序性炎症细胞死亡的术语。细胞焦亡主要分为两种分子信号通路，包括半胱氨酸天冬氨酸蛋白酶-1（caspase-1）依赖性经典途径和半胱氨酸天冬氨酸蛋白酶-4/5/11（caspase-4/5/11）依赖性非经典炎性小体途径。大量研究报告表明，炎性小体的激活促进了白细胞介素-1β/18（IL-1β/18）等炎症因子的成熟和分泌、gasdermin D（GSDMD）的切割，从而刺激细胞焦亡介导的细胞死亡。此外，越来越多的研究表明，NOD 样受体热蛋白结构域 3（NLRP3）炎性小体的激活在触发细胞焦亡介导的细胞死亡中起着重要作用，并促进糖尿病视网膜病变（DR）的发病机制。本综述详细阐述了细胞焦亡信号通路的分子机制及其在 DR 发病机制和影响中的潜在作用。我们还强调了几种调节细胞焦亡死亡关键步骤的研究分子，以产生新的认识和发现，探索 DR 进展的发病机制。我们的叙述性综述简明地提出，这些潜在的药理学药物可能是未来治疗和管理 DR 的有希望的治疗方法。
